Background: Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in gastroenterology. Although PPIs are mostly well tolerated, long-term PPI intake has been linked with diabetes mellitus, osteoporosis and infectious disease. In the present study, we evaluated a potential association between PPI intake and a subsequent diagnosis of liver cancer in a large real-world cohort of outpatients in Germany. Methods: A total of 1766 patients with liver cancer, as well as 8830 propensity-score-matched controls, were identified from the Disease Analyzer database (IQVIA). The outcome of the study was the association between PPI use and a subsequent diagnosis of liver cancer, which was evaluated using multivariable logistic regression analyses. Results: Overall, 42.9% of the liver cancer patients and 39.0% of the controls received at least one PPI prescription before the index date. PPI prescriptions at any time before the index date were associated with an increased risk of subsequent liver cancer (OR: 1.18; 95% CI: 1.06–1.31). The positive association was observed in all age groups, as well as in women and men, but only in women (OR: 1.30; 95% 1.09–1.55) did it reach the predefined level of significance (p< 0.01). When considering the duration of PPI therapy, only PPI therapy for at least two years was significantly associated with an increased risk of liver cancer (OR: 1.28; 95% 1.09–1.50). In an analysis stratified by age and sex, this association was strongest in the age group < 60 years (OR: 1.99; 95% 1.21–3.26). Conclusions: Our data suggest that long-term PPI intake in women as well as in patients < 60 years might be associated with an increased risk of liver cancer. These findings support current efforts to reduce the inappropriate use of PPIs in routine clinical practice and to link PPI prescribing to a clear medical indication.
背景：质子泵抑制剂（PPIs）是胃肠病学领域最常处方的药物之一。尽管PPIs通常耐受性良好，但长期服用与糖尿病、骨质疏松症及感染性疾病风险增加相关。本研究基于德国大型真实世界门诊患者队列，评估了PPI使用与后续肝癌诊断之间的潜在关联。 方法：从疾病分析数据库（IQVIA）中筛选出1766例肝癌患者及8830例倾向评分匹配的对照者。通过多变量逻辑回归分析评估PPI使用与后续肝癌诊断之间的关联。 结果：总体而言，42.9%的肝癌患者和39.0%的对照者在索引日期前至少接受过一次PPI处方。索引日期前任何时间的PPI处方均与后续肝癌风险增加相关（OR：1.18；95% CI：1.06–1.31）。这种正向关联在所有年龄组及不同性别中均被观察到，但仅在女性群体中达到预设显著性水平（OR：1.30；95% CI：1.09–1.55；p<0.01）。当考虑PPI治疗时长时，仅持续至少两年的PPI治疗与肝癌风险显著增加相关（OR：1.28；95% CI：1.09–1.50）。在按年龄和性别分层分析中，这种关联在60岁以下年龄组最为显著（OR：1.99；95% CI：1.21–3.26）。 结论：我们的数据表明，女性及60岁以下患者长期服用PPI可能与肝癌风险增加相关。这些发现支持当前临床实践中减少PPI不当使用、确保处方具有明确医学指征的规范化管理趋势。
肿瘤(癌症)患者之家